Tepotinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of tepotinib.
Drugs List
Therapeutic Indications
Uses
Advanced non-small cell lung cancer (NSCLC) with METex14 mutation
Treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations.
Dosage
Adults
450mg once daily.
Additional Dosage Information
Dose modifications for adverse reactions
The recommended dose reduction for the management of adverse reactions is 225mg daily.
Any grade interstitial lung disease (ILD)
Withhold tepotinib if ILD is suspected. Permanently discontinue tepotinib if ILD is confirmed.
Increased ALT and/or AST without increased total bilirubin
Grade 3: Withhold tepotinib until recovery to baseline ALT/AST. If recovered to baseline within 7 days then resume tepotinib at the same dose, otherwise resume tepotinib at a reduced dose.
Grade 4: Permanently discontinue tepotinib.
Increased ALT and/or AST with increased total bilirubin in the absence of cholestasis or hemolysis
ALT and/or AST greater than 3 x ULN with total bilirubin greater than 2 x ULN: Permanently discontinue tepotinib.
Increased total bilirubin without concurrent increased ALT and/or AST
Grade 3: Withhold tepotinib until recovery to baseline bilirubin. If recovered to baseline within 7 days then resume at a reduced dose, otherwise permanently discontinue.
Grade 4: Permanently discontinue tepotinib.
Other adverse reactions
Grade 2: Maintain dose level. If intolerable, consider withholding tepotinib until resolved, then resume tepotinib at a reduced dose.
Grade 3: Withhold tepotinib until resolved, then resume tepotinib at a reduced dose.
Grade 4: Permanently discontinue tepotinib.
Missed doses
If a dose is missed, it should be taken as soon as remembered on the same day unless the next dose is due within 8 hours.
Contraindications
Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy
Renal impairment - creatinine clearance 15-29ml/minute
Severe hepatic impairment
Precautions and Warnings
Glucose-galactose malabsorption syndrome
Lactose intolerance
Advise ability to drive/operate machinery may be affected by side effects
Confirm METex14 mutation status prior to treatment
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor liver function before, every 2 weeks for 3 months & then monthly
Advise patient to report any new or worsening respiratory symptoms
Discontinue treatment if interstitial lung disease develops
May affect results of some laboratory tests
Discontinue if AST/ALT > 3 x ULN and bilirubin > 2 x ULN
Discontinue permanently if AST or ALT level exceeds 20 x ULN
Discontinue treatment if total bilirubin > 10 x ULN
Interrupt therapy if elevations in bilirubin of > 3 x ULN occur
Interrupt treatment if ALT or AST > 5 x ULN
Suspend treatment if interstitial lung disease is suspected
Permanently discontinue treatment if grade 4 adverse reactions occur
Suspend treatment/reduce dose if grade 3 adverse reactions occur
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 1 week after treatment
Male: Use of condoms required during and for 1 week after treatment
Breastfeeding: Do not breastfeed during & for 1 week after treatment
Interstitial lung disease (ILD)
Patients should be monitored for new or worsening pulmonary symptoms. If ILD is suspected, then tepotinib should be withheld immediately whilst the patient is promptly investigated for alternative diagnosis or specific aetiology of ILD. Tepotinib must be permanently discontinued if ILD is confirmed.
Pregnancy and Lactation
Pregnancy
Tepotinib is contraindicated during pregnancy.
The manufacturer recommends that tepotinib is not used during pregnancy. There are no clinical data of the use of tepotinib in pregnant women. Studies in animals have shown teratogenicity and based on the mechanism of action and findings in animals, it is expected that tepotinib can cause foetal harm in pregnant women.
Lactation
Tepotinib is contraindicated during breastfeeding.
The manufacturer recommends the breastfeeding should be discontinued during treatment with tepotinib and for at least 1 week after the last dose. There are no data regarding whether tepotinib or its metabolites are excreted in human milk, or its effects on the breast-fed infant or milk production.
Side Effects
Abdominal discomfort
Abdominal pain
Acute respiratory distress
Alanine aminotransferase increased
Aspartate aminotransferase increased
Asthenia
Constipation
Diarrhoea
Elevated amylase levels
Elevated serum lipase
Fatigue
Gastro-intestinal pain
Hepatic pain
Hypoalbuminaemia
Increase in alkaline phosphatase
Increase in creatinine
Interstitial lung disease
Nausea
Oedema
Pneumonitis
Vomiting
Effects on Laboratory Tests
Non-clinical studies suggest that tepotinib or its main metabolite inhibit the renal tubular transporter proteins, organic cation transporter (OCT) 2 and multidrug and toxin extrusion transporters (MATE) 1 and 2. Creatinine is a substrate of these two transporters and the observed increases in creatinine in these studies may be the result of the inhibition of active tubular secretion rather than renal impairment. Renal function tests that rely on serum creatinine should be interpreted with caution due to this effect of tepotinib. In cases of increased blood creatinine during tepotinib treatment, it is recommended that further assessment of the renal function should be performed to exclude renal impairment.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: October 2021
Reference Sources
Summary of Product Characteristics: Tepmetko 225mg film-coated tablets. Merck Serono Ltd. Revised September 2021.
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